Influence of Aerobic Training and Weight Loss on Skeletal Muscle Inflammatory Markers and Muscle Protein Balance in Older Adults

Summary

It is estimated that 15% of adults aged 60-70 years, and up to 50% of adults aged 80 years and older are affected by sarcopenia-the age related loss of muscle mass and function. A disruption of the homeostatic balance between periods of muscle protein breakdown (predominant during fasting) and muscle protein synthesis (predominant following nutrient ingestion) can result in the loss of muscle mass over time. In particular, research suggests that an inability of muscle to fully respond to the anabolic influence of nutrient intake may contribute significantly to age-related muscle loss. This anabolic resistance is likely influenced by increased age-related inflammation. There is evidence in cell line and animal models that increased levels of the inflammatory cytokine, tumor necrosis factor-α (TNFα) impairs the molecular pathways that initiate muscle protein synthesis (i.e. mammalian target of rapamycin, mTOR signaling), and can accelerate muscle protein breakdown. Obesity, and sedentary lifestyle have been linked to increased TNFα expression, and thus may partially explain impaired muscle protein balance in older adults. The objectives of this clinical trial are to 1) determine if lifestyle modification via weight loss and aerobic exercise can reduce skeletal muscle inflammation and subsequently improve nutrient-stimulated muscle protein synthesis in previously sedentary, obese older adults; and 2) expose undergraduate Kinesiology and Nutrition majors to meritorious research. The investigators have recently published data with undergraduate researchers showing that body composition is associated with elevated skeletal muscle expression of TNFα converting enzyme (TACE). One of the primary actions of TACE is to cleave membrane bound TNFα (mTNFα) to soluble TNFα (sTNFα)-a more mature and bioactive form of TNFα. Both TACE and sTNFα are known to be elevated in a number of clinical conditions, including heart disease, cancer, arthritis, and diabetes. Based on these data, the investigators feel that TACE may represent an important and potentially modifiable (via weight loss and aerobic conditioning) regulator of skeletal muscle inflammation in humans. There are currently no data on the associations among skeletal muscle expression of TACE, TNFα, and muscle protein balance. Thus, the focus of this study is to determine if 5-10% diet-induced weight loss and 6-months (3 days per week) of aerobic exercise training can influence: 1) TACE and TNFα expression in skeletal muscle; and 2) improve molecular indices of muscle protein breakdown and nutrient-stimulated muscle protein synthesis (mTOR signaling) in sedentary, obese older adults. Specifically, 60 sedentary, obese older adults will be randomized to one of the following groups: 1) control group (CON), 2) a diet-induced weight loss group (DIET), 3) an aerobic exercise training group (EX), or 4) a diet-induced weight loss + aerobic exercise training group (DIET + EX). The results of this study will advance the understanding of the connections among skeletal muscle inflammation and muscle protein balance in older adults, and validate TACE as a potentially modifiable target for the prevention and treatment of sarcopenia and other age-related inflammatory diseases, which will contribute to the development of practice-based guidelines for healthcare practitioners.

Conditions

• Overweight and Obesity
• Inflammation; Muscle
• Sedentary Lifestyle

Interventions

BEHAVIORAL

Diet-Induced Weight Loss

Diet-Induced Weight Loss: The goal of the diet intervention is to produce a weight loss of approximately 5-10% of body weight over the six-month period, which is consistent with the goals for obesity treatment outlined by the Academy of Nutrition and Dietetics (AND). According to the 2016 AND position paper for obesity-related interventions, this level of weight loss produces clinically significant reductions in biometrics (biochemical and anthropometrics measurements) and associated risk factors for chronic disease. Additionally, obese older adults who achieve weight loss intentionally through lifestyle changes experience improved physical function. This intervention will last for 6-months with bi-weekly face-to-face counseling sessions with a registered dietitian.

BEHAVIORAL

Aerobic Exercise Training

Exercise Intervention: Subjects will exercise on a cycle ergometer during the training sessions. Each session will consist of 1) a 5-10 minute warm up at "light" intensity; 2) a 20 to 30-minute training phase at "moderate-to-vigorous" intensity; and 3) a 5-minute cool down phase at "light". The training will be conducted 3 days per week for 6 months.

Sponsors & Collaborators

• Miami University

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

FACTORIAL

Eligibility

Min Age

58 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2018-01-31

Primary Completion

2021-07-30

Completion

2021-09-30

Countries

• United States

Study Locations